Search results for: quinazoline ring
30 Finite Element Analysis of the Anaconda Device: Efficiently Predicting the Location and Shape of a Deployed Stent
Authors: Faidon Kyriakou, William Dempster, David Nash
Abstract:
Abdominal Aortic Aneurysm (AAA) is a major life-threatening pathology for which modern approaches reduce the need for open surgery through the use of stenting. The success of stenting though is sometimes jeopardized by the final position of the stent graft inside the human artery which may result in migration, endoleaks or blood flow occlusion. Herein, a finite element (FE) model of the commercial medical device AnacondaTM (Vascutek, Terumo) has been developed and validated in order to create a numerical tool able to provide useful clinical insight before the surgical procedure takes place. The AnacondaTM device consists of a series of NiTi rings sewn onto woven polyester fabric, a structure that despite its column stiffness is flexible enough to be used in very tortuous geometries. For the purposes of this study, a FE model of the device was built in Abaqus® (version 6.13-2) with the combination of beam, shell and surface elements; the choice of these building blocks was made to keep the computational cost to a minimum. The validation of the numerical model was performed by comparing the deployed position of a full stent graft device inside a constructed AAA with a duplicate set-up in Abaqus®. Specifically, an AAA geometry was built in CAD software and included regions of both high and low tortuosity. Subsequently, the CAD model was 3D printed into a transparent aneurysm, and a stent was deployed in the lab following the steps of the clinical procedure. Images on the frontal and sagittal planes of the experiment allowed the comparison with the results of the numerical model. By overlapping the experimental and computational images, the mean and maximum distances between the rings of the two models were measured in the longitudinal, and the transverse direction and, a 5mm upper bound was set as a limit commonly used by clinicians when working with simulations. The two models showed very good agreement of their spatial positioning, especially in the less tortuous regions. As a result, and despite the inherent uncertainties of a surgical procedure, the FE model allows confidence that the final position of the stent graft, when deployed in vivo, can also be predicted with significant accuracy. Moreover, the numerical model run in just a few hours, an encouraging result for applications in the clinical routine. In conclusion, the efficient modelling of a complicated structure which combines thin scaffolding and fabric has been demonstrated to be feasible. Furthermore, the prediction capabilities of the location of each stent ring, as well as the global shape of the graft, has been shown. This can allow surgeons to better plan their procedures and medical device manufacturers to optimize their designs. The current model can further be used as a starting point for patient specific CFD analysis.Keywords: AAA, efficiency, finite element analysis, stent deployment
Procedia PDF Downloads 18829 An Absolute Femtosecond Rangefinder for Metrological Support in Coordinate Measurements
Authors: Denis A. Sokolov, Andrey V. Mazurkevich
Abstract:
In the modern world, there is an increasing demand for highly precise measurements in various fields, such as aircraft, shipbuilding, and rocket engineering. This has resulted in the development of appropriate measuring instruments that are capable of measuring the coordinates of objects within a range of up to 100 meters, with an accuracy of up to one micron. The calibration process for such optoelectronic measuring devices (trackers and total stations) involves comparing the measurement results from these devices to a reference measurement based on a linear or spatial basis. The reference used in such measurements could be a reference base or a reference range finder with the capability to measure angle increments (EDM). The base would serve as a set of reference points for this purpose. The concept of the EDM for replicating the unit of measurement has been implemented on a mobile platform, which allows for angular changes in the direction of laser radiation in two planes. To determine the distance to an object, a high-precision interferometer with its own design is employed. The laser radiation travels to the corner reflectors, which form a spatial reference with precisely known positions. When the femtosecond pulses from the reference arm and the measuring arm coincide, an interference signal is created, repeating at the frequency of the laser pulses. The distance between reference points determined by interference signals is calculated in accordance with recommendations from the International Bureau of Weights and Measures for the indirect measurement of time of light passage according to the definition of a meter. This distance is D/2 = c/2nF, approximately 2.5 meters, where c is the speed of light in a vacuum, n is the refractive index of a medium, and F is the frequency of femtosecond pulse repetition. The achieved uncertainty of type A measurement of the distance to reflectors 64 m (N•D/2, where N is an integer) away and spaced apart relative to each other at a distance of 1 m does not exceed 5 microns. The angular uncertainty is calculated theoretically since standard high-precision ring encoders will be used and are not a focus of research in this study. The Type B uncertainty components are not taken into account either, as the components that contribute most do not depend on the selected coordinate measuring method. This technology is being explored in the context of laboratory applications under controlled environmental conditions, where it is possible to achieve an advantage in terms of accuracy. In general, the EDM tests showed high accuracy, and theoretical calculations and experimental studies on an EDM prototype have shown that the uncertainty type A of distance measurements to reflectors can be less than 1 micrometer. The results of this research will be utilized to develop a highly accurate mobile absolute range finder designed for the calibration of high-precision laser trackers and laser rangefinders, as well as other equipment, using a 64 meter laboratory comparator as a reference.Keywords: femtosecond laser, pulse correlation, interferometer, laser absolute range finder, coordinate measurement
Procedia PDF Downloads 5128 Hypersensitivity Reactions Following Intravenous Administration of Contrast Medium
Authors: Joanna Cydejko, Paulina Mika
Abstract:
Hypersensitivity reactions are side effects of medications that resemble an allergic reaction. Anaphylaxis is a generalized, severe allergic reaction of the body caused by exposure to a specific agent at a dose tolerated by a healthy body. The most common causes of anaphylaxis are food (about 70%), Hymenoptera venoms (22%), and medications (7%), despite detailed diagnostics in 1% of people, the cause of the anaphylactic reaction was not indicated. Contrast media are anaphylactic agents of unknown mechanism. Hypersensitivity reactions can occur with both immunological and non-immunological mechanisms. Symptoms of anaphylaxis occur within a few seconds to several minutes after exposure to the allergen. Contrast agents are chemical compounds that make it possible to visualize or improve the visibility of anatomical structures. In the diagnosis of computed tomography, the preparations currently used are derivatives of the triiodide benzene ring. Pharmacokinetic and pharmacodynamic properties, i.e., their osmolality, viscosity, low chemotoxicity and high hydrophilicity, have an impact on better tolerance of the substance by the patient's body. In MRI diagnostics, macrocyclic gadolinium contrast agents are administered during examinations. The aim of this study is to present the results of the number and severity of anaphylactic reactions that occurred in patients in all age groups undergoing diagnostic imaging with intravenous administration of contrast agents. In non-ionic iodine CT and in macrocyclic gadolinium MRI. A retrospective assessment of the number of adverse reactions after contrast administration was carried out on the basis of data from the Department of Radiology of the University Clinical Center in Gdańsk, and it was assessed whether their different physicochemical properties had an impact on the incidence of acute complications. Adverse reactions are divided according to the severity of the patient's condition and the diagnostic method used in a given patient. Complications following the administration of a contrast medium in the form of acute anaphylaxis accounted for less than 0.5% of all diagnostic procedures performed with the use of a contrast agent. In the analysis period from January to December 2022, 34,053 CT scans and 15,279 MRI examinations with the use of contrast medium were performed. The total number of acute complications was 21, of which 17 were complications of iodine-based contrast agents and 5 of gadolinium preparations. The introduction of state-of-the-art contrast formulations was an important step toward improving the safety and tolerability of contrast agents used in imaging. Currently, contrast agents administered to patients are considered to be one of the best-tolerated preparations used in medicine. However, like any drug, they can be responsible for the occurrence of adverse reactions resulting from their toxic effects. The increase in the number of imaging tests performed with the use of contrast agents has a direct impact on the number of adverse events associated with their administration. However, despite the low risk of anaphylaxis, this risk should not be marginalized. The growing threat associated with the mass performance of radiological procedures with the use of contrast agents forces the knowledge of the rules of conduct in the event of symptoms of hypersensitivity to these preparations.Keywords: anaphylactic, contrast medium, diagnostic, medical imagine
Procedia PDF Downloads 5427 High Strain Rate Behavior of Harmonic Structure Designed Pure Nickel: Mechanical Characterization Microstructure Analysis and 3D Modelisation
Authors: D. Varadaradjou, H. Kebir, J. Mespoulet, D. Tingaud, S. Bouvier, P. Deconick, K. Ameyama, G. Dirras
Abstract:
The development of new architecture metallic alloys with controlled microstructures is one of the strategic ways for designing materials with high innovation potential and, particularly, with improved mechanical properties as required for structural materials. Indeed, unlike conventional counterparts, metallic materials having so-called harmonic structure displays strength and ductility synergy. The latter occurs due to a unique microstructure design: a coarse grain structure surrounded by a 3D continuous network of ultra-fine grain known as “core” and “shell,” respectively. In the present study, pure harmonic-structured (HS) Nickel samples were processed via controlled mechanical milling and followed by spark plasma sintering (SPS). The present work aims at characterizing the mechanical properties of HS pure Nickel under room temperature dynamic loading through a Split Hopkinson Pressure Bar (SHPB) test and the underlying microstructure evolution. A stopper ring was used to maintain the strain at a fixed value of about 20%. Five samples (named B1 to B5) were impacted using different striker bar velocities from 14 m/s to 28 m/s, yielding strain rate in the range 4000-7000 s-1. Results were considered until a 10% deformation value, which is the deformation threshold for the constant strain rate assumption. The non-deformed (INIT – post-SPS process) and post-SHPB microstructure (B1 to B5) were investigated by EBSD. It was observed that while the strain rate is increased, the average grain size within the core decreases. An in-depth analysis of grains and grain boundaries was made to highlight the thermal (such as dynamic recrystallization) or mechanical (such as grains fragmentation by dislocation) contribution within the “core” and “shell.” One of the most widely used methods for determining the dynamic behavior of materials is the SHPB technique developed by Kolsky. A 3D simulation of the SHPB test was created through ABAQUS in dynamic explicit. This 3D simulation allows taking into account all modes of vibration. An inverse approach was used to identify the material parameters from the equation of Johnson-Cook (JC) by minimizing the difference between the numerical and experimental data. The JC’s parameters were identified using B1 and B5 samples configurations. Predictively, identified parameters of JC’s equation shows good result for the other sample configuration. Furthermore, mean rise of temperature within the harmonic Nickel sample can be obtained through ABAQUS and show an elevation of about 35°C for all fives samples. At this temperature, a thermal mechanism cannot be activated. Therefore, grains fragmentation within the core is mainly due to mechanical phenomena for a fixed final strain of 20%.Keywords: 3D simulation, fragmentation, harmonic structure, high strain rate, Johnson-cook model, microstructure
Procedia PDF Downloads 22326 Algal/Bacterial Membrane Bioreactor for Bioremediation of Chemical Industrial Wastewater Containing 1,4 Dioxane
Authors: Ahmed Tawfik
Abstract:
Oxidation of 1,4 dioxane produces metabolites by-products involving glycolaldehyde and acids that have geno- and cytotoxicity impact on microbial degradation. Thereby, the incorporation of algae with bacteria in the treatment system would eliminate and overcome the accumulation of metabolites that are utilized as a carbon source for the build-up of biomass. Therefore, the aim of the present study is to assess the potential of algae/bacteria-based membrane bioreactor (AB-MBR) for biodegradation of 1,4 dioxane-rich wastewater at a high imposed loading rate. Three identical reactors, i.e., AB-MBR1, AB-MBR2, and AB-MBR3, were operated in parallel at 1,4 dioxane loading rates of 641.7, 320.9, and 160.4 mg/L. d., and HRTs of 6.0, 12 and 24 h. respectively. The AB-MBR1 achieved 1,4 dioxane removal rate of 263.7 mg/L.d., where the residual value in the treated effluent amounted to 94.4±22.9 mg/L. Reducing the 1,4 dioxane loading rate (LR) to 320.9 mg/L.d in the AB-MBR2 maximized the removal rate efficiency of 265.9 mg/L.d., with a removal efficiency of 82.8±3.2%. The minimum value of 1,4 dioxane of 17.3±1.8 mg/L in the treated effluent of AB-MBR3 was obtained at an HRT of 24.0 h and loading rate of 160.4 mg/L.d. The mechanism of 1,4 dioxane degradation in AB-MBR was a combination of volatilization (8.03±0.6%), UV oxidation (14.1±0.9%), microbial biodegradation (49.1±3.9%) and absorption/uptake and assimilation by algae (28.8±2.%). Further, the Thioclava, Afipia, and Mycobacterium genera oxidized and produced the required enzymes for hydrolysis and cleavage of the dioxane ring into 2-hydroxy-1,4 dioxane. Moreover, the fungi, i.e., Basidiomycota and Cryptomycota, played a big role in the degradation of the 1,4 dioxane into 2-hydroxy-1,4 dioxane. Xanthobacter and Mesorhizobium were involved in the metabolism process by secreting alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and glycolate oxidase. Bacteria and fungi produced dehydrogenase (DH) for the transformation of 2-hydroxy-1,4 dioxane into 2-hydroxy-ethoxyacetaldehyde. The latter is converted into Ethylene glycol by Aldehyde hydrogenase (ALDH). Ethylene glycol is oxidized into acids using Alcohol hydrogenase (ADH). The Diatomea, Chlorophyta, and Streptophyta utilize the metabolites for biomass assimilation and produce the required oxygen for further oxidation of the dioxane and its metabolites by-products of bacteria and fungi. The major portion of metabolites (ethylene glycol, glycolic acid, and oxalic acid were removed due to uptake and absorption by algae (43±4.3%), followed by adsorption (18.4±0.9%). The volatilization and UV oxidation contribution for the degradation of metabolites were 8.7±0.7% and 12.3±0.8%, respectively. The capabilities of genera Defluviimonas, Thioclava, Luteolibacter, and Afipia. The genera of Defluviimonas, Thioclava, Luteolibacter, and Mycobacterium were grown under a high 1,4 dioxane LR of 641.7 mg/L.d. The Chlorophyta (4.1-43.6%), Streptophyta (2.5-21.7%), and Diatomea (0.8-1.4%) phyla were dominant for degradation of 1,4 dioxane. The results of this study strongly demonstrated that the bioremediation and bioaugmentation process can safely remove 1,4 dioxane from industrial wastewater while minimizing environmental concerns and reducing economic costs.Keywords: wastewater, membrane bioreactor, bacterial community, algal community
Procedia PDF Downloads 3925 Morphology, Qualitative, and Quantitative Elemental Analysis of Pheasant Eggshells in Thailand
Authors: Kalaya Sribuddhachart, Mayuree Pumipaiboon, Mayuva Youngsabanant-Areekijseree
Abstract:
The ultrastructure of 20 species of pheasant eggshells in Thailand, (Simese Fireback, Lophura diardi), (Silver Pheasant, Lophura nycthemera), (Kalij Pheasant, Lophura leucomelanos crawfurdii), (Kalij Pheasant, Lophura leucomelanos lineata), (Red Junglefowl, Gallus gallus spadiceus), (Crested Fireback, Lophura ignita rufa), (Green Peafowl, Pavo muticus), (Indian Peafowl, Pavo cristatus), (Grey Peacock Pheasant, Polyplectron bicalcaratum bicalcaratum), (Lesser Bornean Fireback, Lophura ignita ignita), (Green Junglefowl, Gallus varius), (Hume's Pheasant, Syrmaticus humiae humiae), (Himalayan Monal, Lophophorus impejanus), Golden Pheasant, Chrysolophus pictus, (Ring-Neck Pheasant, Phasianus sp.), (Reeves’s Pheasant, Syrmaticus reevesi), (Polish Chicken, Gallus sp.), (Brahma Chicken, Gallus sp.), (Yellow Golden Pheasant, Chrysolophus pictus luteus), and (Lady Amhersts Pheasant, Chrysolophus amherstiae) were studied by Secondary electron imaging (SEI) and Energy dispersive X-ray analysis (EDX) detectors of scanning electron microscope. Generally, all pheasant eggshells showed 3 layers of cuticle, palisade, and mammillary. The total thickness was ranging from 190.28±5.94-838.96±16.31µm. The palisade layer is the most thickness layer following by mammillary and cuticle layers. The palisade layer in all pheasant eggshells consisted of numerous vesicle holes that were firmly forming as network thorough the layer. The vesicle holes in all pheasant eggshells had difference porosity ranging from 0.44±0.11-0.23±0.05 µm. While the mammillary layer was the most compact layer with a variable shape (broad-base V and U-shape) connect to shell membrane. Elemental analysis by of 20 specie eggshells showed 9 apparent elements including carbon (C), oxygen (O), calcium (Ca), phosphorous (P), sulfur (S), magnesium (Mg), silicon (Si), aluminum (Al), and copper (Cu) at the percentage of 28.90- 8.33%, 60.64-27.61%, 55.30-14.49%, 1.97-0.03%, 0.08-0.03%, 0.50-0.16%, 0.30-0.04%, 0.06-0.02%, and 2.67-1.73%, respectively. It was found that Ca, C, and O showed highest elemental compositions, which essential for pheasant embryonic development, mainly presented as composited structure of calcium carbonate (CaCO3) more than 97%. Meanwhile, Mg, S, Si, Al, and P were major inorganic constituents of the eggshells which directly related to an increase of the shell hardness. Finally, the percentage of heavy metal copper (Cu) has been observed in 4 eggshell species. There are Golden Pheasant (2.67±0.16%), Indian Peafowl (2.61±0.13%), Green Peafowl (1.97±0.74%), and Silver Pheasant (1.73±0.11%), respectively. A non-significant difference was found in the percentages of 9 elements in all pheasant eggshells. This study is useful to provide the information of biology and taxonomic of pheasant study in Thailand for conservation.Keywords: pheasants eggshells, secondary electron imaging (SEI) and energy dispersive X-ray analysis (EDX), morphology, Thailand
Procedia PDF Downloads 23024 Drivers of Satisfaction and Dissatisfaction in Camping Tourism: A Case Study from Croatia
Authors: Darko Prebežac, Josip Mikulić, Maja Šerić, Damir Krešić
Abstract:
Camping tourism is recognized as a growing segment of the broader tourism industry, currently evolving from an inexpensive, temporary sojourn in a rural environment into a highly fragmented niche tourism sector. The trends among public-managed campgrounds seem to be moving away from rustic campgrounds that provide only a tent pad and a fire ring to more developed facilities that offer a range of different amenities, where campers still search for unique experiences that go above the opportunity to experience nature and social interaction. In addition, while camping styles and options changed significantly over the last years, coastal camping in particular became valorized as is it regarded with a heightened sense of nostalgia. Alongside this growing interest in the camping tourism, a demand for quality servicing infrastructure emerged in order to satisfy the wide variety of needs, wants, and expectations of an increasingly demanding traveling public. However, camping activity in general and quality of camping experience and campers’ satisfaction in particular remain an under-researched area of the tourism and consumption behavior literature. In this line, very few studies addressed the issue of quality product/service provision in satisfying nature based tourists and in driving their future behavior with respect to potential re-visitation and recommendation intention. The present study thus aims to investigate the drivers of positive and negative campsite experience using the case of Croatia. Due to the well-preserved nature and indented coastline, camping tourism has a long tradition in Croatia and represents one of the most important and most developed tourism products. During the last decade the number of tourist overnights in Croatian camps has increased by 26% amounting to 16.5 million in 2014. Moreover, according to Eurostat the market share of campsites in the EU is around 14%, indicating that the market share of Croatian campsites is almost double large compared to the EU average. Currently, there are a total of 250 camps in Croatia with approximately 75.8 thousands accommodation units. It is further noteworthy that Croatian camps have higher average occupancy rates and a higher average length of stay as compared to the national average of all types of accommodation. In order to explore the main drivers of positive and negative campsite experiences, this study uses principal components analysis (PCA) and an impact-asymmetry analysis (IAA). Using the PCA, first the main dimensions of the campsite experience are extracted in an exploratory manner. Using the IAA, the extracted factors are investigated for their potentials to create customer delight and/or frustration. The results provide valuable insight to both researchers and practitioners regarding the understanding of campsite satisfaction.Keywords: Camping tourism, campsite, impact-asymmetry analysis, satisfaction
Procedia PDF Downloads 18123 Electro-Hydrodynamic Effects Due to Plasma Bullet Propagation
Authors: Panagiotis Svarnas, Polykarpos Papadopoulos
Abstract:
Atmospheric-pressure cold plasmas continue to gain increasing interest for various applications due to their unique properties, like cost-efficient production, high chemical reactivity, low gas temperature, adaptability, etc. Numerous designs have been proposed for these plasmas production in terms of electrode configuration, driving voltage waveform and working gas(es). However, in order to exploit most of the advantages of these systems, the majority of the designs are based on dielectric-barrier discharges (DBDs) either in filamentary or glow regimes. A special category of the DBD-based atmospheric-pressure cold plasmas refers to the so-called plasma jets, where a carrier noble gas is guided by the dielectric barrier (usually a hollow cylinder) and left to flow up to the atmospheric air where a complicated hydrodynamic interplay takes place. Although it is now well established that these plasmas are generated due to ionizing waves reminding in many ways streamer propagation, they exhibit discrete characteristics which are better mirrored on the terms 'guided streamers' or 'plasma bullets'. These 'bullets' travel with supersonic velocities both inside the dielectric barrier and the channel formed by the noble gas during its penetration into the air. The present work is devoted to the interpretation of the electro-hydrodynamic effects that take place downstream of the dielectric barrier opening, i.e., in the noble gas-air mixing area where plasma bullet propagate under the influence of local electric fields in regions of variable noble gas concentration. Herein, we focus on the role of the local space charge and the residual ionic charge left behind after the bullet propagation in the gas flow field modification. The study communicates both experimental and numerical results, coupled in a comprehensive manner. The plasma bullets are here produced by a custom device having a quartz tube as a dielectric barrier and two external ring-type electrodes driven by sinusoidal high voltage at 10 kHz. Helium gas is fed to the tube and schlieren photography is employed for mapping the flow field downstream of the tube orifice. Mixture mass conservation equation, momentum conservation equation, energy conservation equation in terms of temperature and helium transfer equation are simultaneously solved, leading to the physical mechanisms that govern the experimental results. Namely, we deal with electro-hydrodynamic effects mainly due to momentum transfer from atomic ions to neutrals. The atomic ions are left behind as residual charge after the bullet propagation and gain energy from the locally created electric field. The electro-hydrodynamic force is eventually evaluated.Keywords: atmospheric-pressure plasmas, dielectric-barrier discharges, schlieren photography, electro-hydrodynamic force
Procedia PDF Downloads 13422 The Structural Alteration of DNA Native Structure of Staphylococcus aureus Bacteria by Designed Quinoxaline Small Molecules Result in Their Antibacterial Properties
Authors: Jeet Chakraborty, Sanjay Dutta
Abstract:
Antibiotic resistance by bacteria has proved to be a severe threat to mankind in recent times, and this fortifies an urgency to design and develop potent antibacterial small molecules/compounds with nonconventional mechanisms than the conventional ones. DNA carries the genetic signature of any organism, and bacteria maintain their genomic DNA inside the cell in a well-regulated compact form with the help of various nucleoid associated proteins like HU, HNS, etc. These proteins control various fundamental processes like gene expression, replication, etc., inside the cell. Alteration of the native DNA structure of bacteria can lead to severe consequences in cellular processes inside the bacterial cell that ultimately result in the death of the organism. The change in the global DNA structure by small molecules initiates a plethora of cellular responses that have not been very well investigated. Echinomycin and Triostin-A are biologically active Quinoxaline small molecules that typically consist of a quinoxaline chromophore attached with an octadepsipeptide ring. They bind to double-stranded DNA in a sequence-specific way and have high activity against a wide variety of bacteria, mainly against Gram-positive ones. To date, few synthetic quinoxaline scaffolds were synthesized, displaying antibacterial potential against a broad scale of pathogenic bacteria. QNOs (Quinoxaline N-oxides) are known to target DNA and instigate reactive oxygen species (ROS) production in bacteria, thereby exhibiting antibacterial properties. The divergent role of Quinoxaline small molecules in medicinal research qualifies them for the evaluation of their antimicrobial properties as a potential candidate. The previous study from our lab has given new insights on a 6-nitroquinoxaline derivative 1d as an intercalator of DNA, which induces conformational changes in DNA upon binding.7 The binding event observed was dependent on the presence of a crucial benzyl substituent on the quinoxaline moiety. This was associated with a large induced CD (ICD) appearing in a sigmoidal pattern upon the interaction of 1d with dsDNA. The induction of DNA superstructures by 1d at high Drug:DNA ratios was observed that ultimately led to DNA condensation. Eviction of invitro-assembled nucleosome upon treatment with a high dose of 1d was also observed. In this work, monoquinoxaline derivatives of 1d were synthesized by various modifications of the 1d scaffold. The set of synthesized 6-nitroquinoxaline derivatives along with 1d were all subjected to antibacterial evaluation across five different bacteria species. Among the compound set, 3a displayed potent antibacterial activity against Staphylococcus aureus bacteria. 3a was further subjected to various biophysical studies to check whether the DNA structural alteration potential was still intact. The biological response of S. aureus cells upon treatment with 3a was studied using various cell biology processes, which led to the conclusion that 3d can initiate DNA damage in the S. aureus cells. Finally, the potential of 3a in disrupting preformed S.aureus and S.epidermidis biofilms was also studied.Keywords: DNA structural change, antibacterial, intercalator, DNA superstructures, biofilms
Procedia PDF Downloads 16421 Considering Aerosol Processes in Nuclear Transport Package Containment Safety Cases
Authors: Andrew Cummings, Rhianne Boag, Sarah Bryson, Gordon Turner
Abstract:
Packages designed for transport of radioactive material must satisfy rigorous safety regulations specified by the International Atomic Energy Agency (IAEA). Higher Activity Waste (HAW) transport packages have to maintain containment of their contents during normal and accident conditions of transport (NCT and ACT). To ensure containment criteria is satisfied these packages are required to be leak-tight in all transport conditions to meet allowable activity release rates. Package design safety reports are the safety cases that provide the claims, evidence and arguments to demonstrate that packages meet the regulations and once approved by the competent authority (in the UK this is the Office for Nuclear Regulation) a licence to transport radioactive material is issued for the package(s). The standard approach to demonstrating containment in the RWM transport safety case is set out in BS EN ISO 12807. In this document a method for measuring a leak rate from the package is explained by way of a small interspace test volume situated between two O-ring seals on the underside of the package lid. The interspace volume is pressurised and a pressure drop measured. A small interspace test volume makes the method more sensitive enabling the measurement of smaller leak rates. By ascertaining the activity of the contents, identifying a releasable fraction of material and by treating that fraction of material as a gas, allowable leak rates for NCT and ACT are calculated. The adherence to basic safety principles in ISO12807 is very pessimistic and current practice in the demonstration of transport safety, which is accepted by the UK regulator. It is UK government policy that management of HAW will be through geological disposal. It is proposed that the intermediate level waste be transported to the geological disposal facility (GDF) in large cuboid packages. This poses a challenge for containment demonstration because such packages will have long seals and therefore large interspace test volumes. There is also uncertainty on the releasable fraction of material within the package ullage space. This is because the waste may be in many different forms which makes it difficult to define the fraction of material released by the waste package. Additionally because of the large interspace test volume, measuring the calculated leak rates may not be achievable. For this reason a justification for a lower releasable fraction of material is sought. This paper considers the use of aerosol processes to reduce the releasable fraction for both NCT and ACT. It reviews the basic coagulation and removal processes and applies the dynamic aerosol balance equation. The proposed solution includes only the most well understood physical processes namely; Brownian coagulation and gravitational settling. Other processes have been eliminated either on the basis that they would serve to reduce the release to the environment further (pessimistically in keeping with the essence of nuclear transport safety cases) or that they are not credible in the conditions of transport considered.Keywords: aerosol processes, Brownian coagulation, gravitational settling, transport regulations
Procedia PDF Downloads 11220 Parametric Study for Obtaining the Structural Response of Segmental Tunnels in Soft Soil by Using No-Linear Numerical Models
Authors: Arturo Galván, Jatziri Y. Moreno-Martínez, Israel Enrique Herrera Díaz, José Ramón Gasca Tirado
Abstract:
In recent years, one of the methods most used for the construction of tunnels in soft soil is the shield-driven tunneling. The advantage of this construction technique is that it allows excavating the tunnel while at the same time a primary lining is placed, which consists of precast segments. There are joints between segments, also called longitudinal joints, and joints between rings (called as circumferential joints). This is the reason because of this type of constructions cannot be considered as a continuous structure. The effect of these joints influences in the rigidity of the segmental lining and therefore in its structural response. A parametric study was performed to take into account the effect of different parameters in the structural response of typical segmental tunnels built in soft soil by using non-linear numerical models based on Finite Element Method by means of the software package ANSYS v. 11.0. In the first part of this study, two types of numerical models were performed. In the first one, the segments were modeled by using beam elements based on Timoshenko beam theory whilst the segment joints were modeled by using inelastic rotational springs considering the constitutive moment-rotation relation proposed by Gladwell. In this way, the mechanical behavior of longitudinal joints was simulated. On the other hand for simulating the mechanical behavior of circumferential joints elastic springs were considered. As well as, the stability given by the soil was modeled by means of elastic-linear springs. In the second type of models, the segments were modeled by means of three-dimensional solid elements and the joints with contact elements. In these models, the zone of the joints is modeled as a discontinuous (increasing the computational effort) therefore a discrete model is obtained. With these contact elements the mechanical behavior of joints is simulated considering that when the joint is closed, there is transmission of compressive and shear stresses but not of tensile stresses and when the joint is opened, there is no transmission of stresses. This type of models can detect changes in the geometry because of the relative movement of the elements that form the joints. A comparison between the numerical results with two types of models was carried out. In this way, the hypothesis considered in the simplified models were validated. In addition, the numerical models were calibrated with (Lab-based) experimental results obtained from the literature of a typical tunnel built in Europe. In the second part of this work, a parametric study was performed by using the simplified models due to less used computational effort compared to complex models. In the parametric study, the effect of material properties, the geometry of the tunnel, the arrangement of the longitudinal joints and the coupling of the rings were studied. Finally, it was concluded that the mechanical behavior of segment and ring joints and the arrangement of the segment joints affect the global behavior of the lining. As well as, the effect of the coupling between rings modifies the structural capacity of the lining.Keywords: numerical models, parametric study, segmental tunnels, structural response
Procedia PDF Downloads 22319 Impact of Insect-Feeding and Fire-Heating Wounding on Wood Properties of Lodgepole Pine
Authors: Estelle Arbellay, Lori D. Daniels, Shawn D. Mansfield, Alice S. Chang
Abstract:
Mountain pine beetle (MPB) outbreaks are currently devastating lodgepole pine forests in western North America, which are also widely disturbed by frequent wildfires. Both MPB and fire can leave scars on lodgepole pine trees, thereby diminishing their commercial value and possibly compromising their utilization in solid wood products. In order to fully exploit the affected resource, it is crucial to understand how wounding from these two disturbance agents impact wood properties. Moreover, previous research on lodgepole pine has focused solely on sound wood and stained wood resulting from the MPB-transmitted blue fungi. By means of a quantitative multi-proxy approach, we tested the hypotheses that (i) wounding (of either MPB or fire origin) caused significant changes in wood properties of lodgepole pine and that (ii) MPB-induced wound effects could differ from those induced by fire in type and magnitude. Pith-to-bark strips were extracted from 30 MPB scars and 30 fire scars. Strips were cut immediately adjacent to the wound margin and encompassed 12 rings from normal wood formed prior to wounding and 12 rings from wound wood formed after wounding. Wood properties evaluated within this 24-year window included ring width, relative wood density, cellulose crystallinity, fibre dimensions, and carbon and nitrogen concentrations. Methods used to measure these proxies at a (sub-)annual resolution included X-ray densitometry, X-ray diffraction, fibre quality analysis, and elemental analysis. Results showed a substantial growth release in wound wood compared to normal wood, as both earlywood and latewood width increased over a decade following wounding. Wound wood was also shown to have a significantly different latewood density than normal wood 4 years after wounding. Latewood density decreased in MPB scars while the opposite was true in fire scars. By contrast, earlywood density was presented only minor variations following wounding. Cellulose crystallinity decreased in wound wood compared to normal wood, being especially diminished in MPB scars the first year after wounding. Fibre dimensions also decreased following wounding. However, carbon and nitrogen concentrations did not substantially differ between wound wood and normal wood. Nevertheless, insect-feeding and fire-heating wounding were shown to significantly alter most wood properties of lodgepole pine, as demonstrated by the existence of several morphological anomalies in wound wood. MPB and fire generally elicited similar anomalies, with the major exception of latewood density. In addition to providing quantitative criteria for differentiating between biotic (MPB) and abiotic (fire) disturbances, this study provides the wood industry with fundamental information on the physiological response of lodgepole pine to wounding in order to evaluate the utilization of scarred trees in solid wood products.Keywords: elemental analysis, fibre quality analysis, lodgepole pine, wood properties, wounding, X-ray densitometry, X-ray diffraction
Procedia PDF Downloads 31318 The Effects of Bisphosphonates on Osteonecrosis of Jaw Bone: A Stem Cell Perspective
Authors: Huseyin Apdik, Aysegul Dogan, Selami Demirci, Ezgi Avsar Apdik, Fikrettin Sahin
Abstract:
Mesenchymal stem cells (MSCs) are crucial cell types for bone maintenance and growth along with resident bone progenitor cells providing bone tissue integrity during osteogenesis and skeletal growth. Any deficiency in this regulation would result in vital bone diseases. Of those, osteoporosis, characterized by a reduction in bone mass and mineral density, is a critical skeletal disease for especially elderly people. The commonly used drugs for the osteoporosis treatment are bisphosphonates (BPs). The most prominent role of BPs is to prevent bone resorption arisen from high osteoclast activity. However, administrations of bisphosphonates may also cause bisphosphonate-induced osteonecrosis of the jaw (BIONJ). Up to the present, the researchers have proposed several circumstances for BIONJ. However, effects of long-term and/or high dose usage of BPs on stem cell’s proliferation, survival, differentiation or maintenance capacity have not been evaluated yet. The present study will be held to; figure out BPs’ effects on MSCs in vitro in the aspect of cell proliferation and toxicity, migration, angiogenic activity, lineage specific gene and protein expression levels, mesenchymal stem cell properties and potential signaling pathways affected by BP treatment. Firstly, mesenchymal stem cell characteristics of Dental Pulp Stem Cells (DPSCs) and Periodontal Ligament Stem Cells (PDLSCs) were proved using flow cytometry analysis. Cell viability analysis was completed to determine the cytotoxic effects of BPs (Zoledronate (Zol), Alendronate (Ale) and Risedronate (Ris)) on DPSCs and PDLSCs by the 3-(4,5-di-methyl-thiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium (MTS) assay. Non-toxic concentrations of BPs were determined at 24 h under growth condition, and at 21 days under osteogenic differentiation condition for both cells. The scratch assay was performed to evaluate their migration capacity under the usage of determined of BPs concentrations at 24 h. The results revealed that while the scratch closure is 70% in the control group for DPSCs, it was 57%, 66% and 66% in Zol, Ale and Ris groups, respectively. For PDLSs, while wound closure is 71% in control group, it was 65%, 66% and 66% in Zol, Ale and Ris groups, respectively. As future experiments, tube formation assay and aortic ring assay will be done to determinate angiogenesis abilities of DPSCs and PDLSCs treated with BPs. Expression levels of osteogenic differentiation marker genes involved in bone development will be determined using real time-polymerase change reaction (RT-PCR) assay and expression profiles of important proteins involved in osteogenesis will be evaluated using western blotting assay for osteogenically differentiated MSCs treated with or without BPs. In addition to these, von Kossa staining will be performed to measure calcium mineralization status of MSCs.Keywords: bisphosphonates, bisphosphonate-induced osteonecrosis of the jaw, mesenchymal stem cells, osteogenesis
Procedia PDF Downloads 25817 Charged Amphiphilic Polypeptide Based Micelle Hydrogel Composite for Dual Drug Release
Authors: Monika Patel, Kazuaki Matsumura
Abstract:
Synthetic hydrogels, with their unique properties such as porosity, strength, and swelling in aqueous environment, are being used in many fields from food additives to regenerative medicines, from diagnostic and pharmaceuticals to drug delivery systems (DDS). But, hydrogels also have some limitations in terms of homogeneity of drug distribution and quantity of loaded drugs. As an alternate, polymeric micelles are extensively used as DDS. With the ease of self-assembly, and distinct stability they remarkably improve the solubility of hydrophobic drugs. However, presently, combinational therapy is the need of time and so are systems which are capable of releasing more than one drug. And it is one of the major challenges towards DDS to control the release of each drug independently, which simple DDS cannot meet. In this work, we present an amphiphilic polypeptide based micelle hydrogel composite to study the dual drug release for wound healing purposes using Amphotericin B (AmpB) and Curcumin as model drugs. Firstly, two differently charged amphiphilic polypeptide chains were prepared namely, poly L-Lysine-b-poly phenyl alanine (PLL-PPA) and poly Glutamic acid-b-poly phenyl alanine (PGA-PPA) through ring opening polymerization of amino acid N-carboxyanhydride. These polymers readily self-assemble to form micelles with hydrophobic PPA block as core and hydrophilic PLL/PGA as shell with an average diameter of about 280nm. The thus formed micelles were loaded with the model drugs. The PLL-PPA micelle was loaded with curcumin and PGA-PPA was loaded with AmpB by dialysis method. Drug loaded micelles showed a slight increase in the mean diameter and were fairly stable in solution and lyophilized forms. For forming the micelles hydrogel composite, the drug loaded micelles were dissolved and were cross linked using genipin. Genipin uses the free –NH2 groups in the PLL-PPA micelles to form a hydrogel network with free PGA-PPA micelles trapped in between the 3D scaffold formed. Different composites were tested by changing the weight ratios of the both micelles and were seen to alter its resulting surface charge from positive to negative with increase in PGA-PPA ratio. The composites with high surface charge showed a burst release of drug in initial phase, were as the composites with relatively low net charge showed a sustained release. Thus the resultant surface charge of the composite can be tuned to tune its drug release profile. Also, while studying the degree of cross linking among the PLL-PPA particles for effect on dual drug release, it was seen that as the degree of crosslinking increases, an increase in the tendency to burst release the drug (AmpB) is seen in PGA-PPA particle, were as on the contrary the PLL-PPA particles showed a slower release of Curcumin with increasing the cross linking density. Thus, two different pharmacokinetic profile of drugs were seen by changing the cross linking degree. In conclusion, a unique charged amphiphilic polypeptide based micelle hydrogel composite for dual drug delivery. This composite can be finely tuned on the basis of need of drug release profiles by changing simple parameters such as composition, cross linking and pH.Keywords: amphiphilic polypeptide, dual drug release, micelle hydrogel composite, tunable DDS
Procedia PDF Downloads 20316 Assessment of Biofilm Production Capacity of Industrially Important Bacteria under Electroinductive Conditions
Authors: Omolola Ojetayo, Emmanuel Garuba, Obinna Ajunwa, Abiodun A. Onilude
Abstract:
Introduction: Biofilm is a functional community of microorganisms that are associated with a surface or an interface. These adherent cells become embedded within an extracellular matrix composed of polymeric substances, i.e., biofilms refer to biological deposits consisting of both microbes and their extracellular products on biotic and abiotic surfaces. Despite their detrimental effects in medicine, biofilms as natural cell immobilization have found several applications in biotechnology, such as in the treatment of wastewater, bioremediation and biodegradation, desulfurization of gas, and conversion of agro-derived materials into alcohols and organic acids. The means of enhancing immobilized cells have been chemical-inductive, and this affects the medium composition and final product. Physical factors including electrical, magnetic, and electromagnetic flux have shown potential for enhancing biofilms depending on the bacterial species, nature, and intensity of emitted signals, the duration of exposure, and substratum used. However, the concept of cell immobilisation by electrical and magnetic induction is still underexplored. Methods: To assess the effects of physical factors on biofilm formation, six American typed culture collection (Acetobacter aceti ATCC15973, Pseudomonas aeruginosa ATCC9027, Serratia marcescens ATCC14756, Gluconobacter oxydans ATCC19357, Rhodobacter sphaeroides ATCC17023, and Bacillus subtilis ATCC6633) were used. Standard culture techniques for bacterial cells were adopted. Natural autoimmobilisation potentials of test bacteria were carried out by simple biofilms ring formation on tubes, while crystal violet binding assay techniques were adopted in the characterisation of biofilm quantity. Electroinduction of bacterial cells by direct current (DC) application in cell broth, static magnetic field exposure, and electromagnetic flux were carried out, and autoimmobilisation of cells in a biofilm pattern was determined on various substrata tested, including wood, glass, steel, polyvinylchloride (PVC) and polyethylene terephthalate. Biot Savart law was used in quantifying magnetic field intensity, and statistical analyses of data obtained were carried out using the analyses of variance (ANOVA) as well as other statistical tools. Results: Biofilm formation by the selected test bacteria was enhanced by the physical factors applied. Electromagnetic induction had the greatest effect on biofilm formation, with magnetic induction producing the least effect across all substrata used. Microbial cell-cell communication could be a possible means via which physical signals affected the cells in a polarisable manner. Conclusion: The enhancement of biofilm formation by bacteria using physical factors has shown that their inherent capability as a cell immobilization method can be further optimised for industrial applications. A possible relationship between the presence of voltage-dependent channels, mechanosensitive channels, and bacterial biofilms could shed more light on this phenomenon.Keywords: bacteria, biofilm, cell immobilization, electromagnetic induction, substrata
Procedia PDF Downloads 18215 Increased Stability of Rubber-Modified Asphalt Mixtures to Swelling, Expansion and Rebound Effect during Post-Compaction
Authors: Fernando Martinez Soto, Gaetano Di Mino
Abstract:
The application of rubber into bituminous mixtures requires attention and care during mixing and compaction. Rubber modifies the properties because it reacts in the internal structure of bitumen at high temperatures changing the performance of the mixture (interaction process of solvents with binder-rubber aggregate). The main change is the increasing of the viscosity and elasticity of the binder due to the larger sizes of the rubber particles by dry process but, this positive effect is counteracted by short mixing times, compared to wet technology, and due to the transport processes, curing time and post-compaction of the mixtures. Therefore, negative effects as swelling of rubber particles, rebounding effect of the specimens and thermal changes by different expansion of the structure inside the mixtures, can change the mechanical properties of the rubberized blends. Based on the dry technology, different asphalt-rubber binders using devulcanized or natural rubber (truck and bus tread rubber), have served to demonstrate these effects and how to solve them into two dense-gap graded rubber modified asphalt concrete mixes (RUMAC) to enhance the stability, workability and durability of the compacted samples by Superpave gyratory compactor method. This paper specifies the procedures developed in the Department of Civil Engineering of the University of Palermo during September 2016 to March 2017, for characterizing the post-compaction and mix-stability of the one conventional mixture (hot mix asphalt without rubber) and two gap-graded rubberized asphalt mixes according granulometry for rail sub-ballast layers with nominal size of Ø22.4mm of aggregates according European standard. Thus, the main purpose of this laboratory research is the application of ambient ground rubber from scrap tires processed at conventional temperature (20ºC) inside hot bituminous mixtures (160-220ºC) as a substitute for 1.5%, 2% and 3% by weight of the total aggregates (3.2%, 4.2% and, 6.2% respectively by volumetric part of the limestone aggregates of bulk density equal to 2.81g/cm³) considered, not as a part of the asphalt binder. The reference bituminous mixture was designed with 4% of binder and ± 3% of air voids, manufactured for a conventional bitumen B50/70 at 160ºC-145ºC mix-compaction temperatures to guarantee the workability of the mixes. The proportions of rubber proposed are #60-40% for mixtures with 1.5 to 2% of rubber and, #20-80% for mixture with 3% of rubber (as example, a 60% of Ø0.4-2mm and 40% of Ø2-4mm). The temperature of the asphalt cement is between 160-180 ºC for mixing and 145-160 ºC for compaction, according to the optimal values for viscosity using Brookfield viscometer and 'ring and ball' - penetration tests. These crumb rubber particles act as a rubber-aggregate into the mixture, varying sizes between 0.4mm to 2mm in a first fraction, and 2-4mm as second proportion. Ambient ground rubber with a specific gravity of 1.154g/cm³ is used. The rubber is free of loose fabric, wire, and other contaminants. It was found optimal results in real beams and cylindrical specimens with each HMA mixture reducing the swelling effect. Different factors as temperature, particle sizes of rubber, number of cycles and pressures of compaction that affect the interaction process are explained.Keywords: crumb-rubber, gyratory compactor, rebounding effect, superpave mix-design, swelling, sub-ballast railway
Procedia PDF Downloads 24014 Structural Molecular Dynamics Modelling of FH2 Domain of Formin DAAM
Authors: Rauan Sakenov, Peter Bukovics, Peter Gaszler, Veronika Tokacs-Kollar, Beata Bugyi
Abstract:
FH2 (formin homology-2) domains of several proteins, collectively known as formins, including DAAM, DAAM1 and mDia1, promote G-actin nucleation and elongation. FH2 domains of these formins exist as oligomers. Chain dimerization by ring structure formation serves as a structural basis for actin polymerization function of FH2 domain. Proper single chain configuration and specific interactions between its various regions are necessary for individual chains to form a dimer functional in G-actin nucleation and elongation. FH1 and WH2 domain-containing formins were shown to behave as intrinsically disordered proteins. Thus, the aim of this research was to study structural dynamics of FH2 domain of DAAM. To investigate structural features of FH2 domain of DAAM, molecular dynamics simulation of chain A of FH2 domain of DAAM solvated in water box in 50 mM NaCl was conducted at temperatures from 293.15 to 353.15K, with VMD 1.9.2, NAMD 2.14 and Amber Tools 21 using 2z6e and 1v9d PDB structures of DAAM was obtained on I-TASSER webserver. Calcium and ATP bound G-actin 3hbt PDB structure was used as a reference protein with well-described structural dynamics of denaturation. Topology and parameter information of CHARMM 2012 additive all-atom force fields for proteins, carbohydrate derivatives, water and ions were used in NAMD 2.14 and ff19SB force field for proteins in Amber Tools 21. The systems were energy minimized for the first 1000 steps, equilibrated and produced in NPT ensemble for 1ns using stochastic Langevin dynamics and the particle mesh Ewald method. Our root-mean square deviation (RMSD) analysis of molecular dynamics of chain A of FH2 domains of DAAM revealed similar insignificant changes of total molecular average RMSD values of FH2 domain of these formins at temperatures from 293.15 to 353.15K. In contrast, total molecular average RMSD values of G-actin showed considerable increase at 328K, which corresponds to the denaturation of G-actin molecule at this temperature and its transition from native, ordered, to denatured, disordered, state which is well-described in the literature. RMSD values of lasso and tail regions of chain A of FH2 domain of DAAM exhibited higher than total molecular average RMSD at temperatures from 293.15 to 353.15K. These regions are functional in intra- and interchain interactions and contain highly conserved tryptophan residues of lasso region, highly conserved GNYMN sequence of post region and amino acids of the shell of hydrophobic pocket of the salt bridge between Arg171 and Asp321, which are important for structural stability and ordered state of FH2 domain of DAAM and its functions in FH2 domain dimerization. In conclusion, higher than total molecular average RMSD values of lasso and post regions of chain A of FH2 domain of DAAM may explain disordered state of FH2 domain of DAAM at temperatures from 293.15 to 353.15K. Finally, absence of marked transition, in terms of significant changes in average molecular RMSD values between native and denatured states of FH2 domain of DAAM at temperatures from 293.15 to 353.15K, can make it possible to attribute these formins to the group of intrinsically disordered proteins rather than to the group of intrinsically ordered proteins such as G-actin.Keywords: FH2 domain, DAAM, formins, molecular modelling, computational biophysics
Procedia PDF Downloads 12913 Comparison of On-Site Stormwater Detention Policies in Australian and Brazilian Cities
Authors: Pedro P. Drumond, James E. Ball, Priscilla M. Moura, Márcia M. L. P. Coelho
Abstract:
In recent decades, On-site Stormwater Detention (OSD) systems have been implemented in many cities around the world. In Brazil, urban drainage source control policies were created in the 1990’s and were mainly based on OSD. The concept of this technique is to promote the detention of additional stormwater runoff caused by impervious areas, in order to maintain pre-urbanization peak flow levels. In Australia OSD, was first adopted in the early 1980’s by the Ku-ring-gai Council in Sydney’s northern suburbs and Wollongong City Council. Many papers on the topic were published at that time. However, source control techniques related to stormwater quality have become to the forefront and OSD has been relegated to the background. In order to evaluate the effectiveness of the current regulations regarding OSD, the existing policies were compared in Australian cities, a country considered experienced in the use of this technique, and in Brazilian cities where OSD adoption has been increasing. The cities selected for analysis were Wollongong and Belo Horizonte, the first municipalities to adopt OSD in their respective countries, and Sydney and Porto Alegre, cities where these policies are local references. The Australian and Brazilian cities are located in Southern Hemisphere of the planet and similar rainfall intensities can be observed, especially in storm bursts greater than 15 minutes. Regarding technical criteria, Brazilian cities have a site-based approach, analyzing only on-site system drainage. This approach is criticized for not evaluating impacts on urban drainage systems and in rare cases may cause the increase of peak flows downstream. The city of Wollongong and most of the Sydney Councils adopted a catchment-based approach, requiring the use of Permissible Site Discharge (PSD) and Site Storage Requirements (SSR) values based on analysis of entire catchments via hydrograph-producing computer models. Based on the premise that OSD should be designed to dampen storms of 100 years Average Recurrence Interval (ARI) storm, the values of PSD and SSR in these four municipalities were compared. In general, Brazilian cities presented low values of PSD and high values of SSR. This can be explained by site-based approach and the low runoff coefficient value adopted for pre-development conditions. The results clearly show the differences between approaches and methodologies adopted in OSD designs among Brazilian and Australian municipalities, especially with regard to PSD values, being on opposite sides of the scale. However, lack of research regarding the real performance of constructed OSD does not allow for determining which is best. It is necessary to investigate OSD performance in a real situation, assessing the damping provided throughout its useful life, maintenance issues, debris blockage problems and the parameters related to rain-flow methods. Acknowledgments: The authors wish to thank CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico (Chamada Universal – MCTI/CNPq Nº 14/2014), FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais, and CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior for their financial support.Keywords: on-site stormwater detention, source control, stormwater, urban drainage
Procedia PDF Downloads 17412 Leveraging the HDAC Inhibitory Pharmacophore to Construct Deoxyvasicinone Based Tractable Anti-Lung Cancer Agent and pH-Responsive Nanocarrier
Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali
Abstract:
A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles
Procedia PDF Downloads 9011 Identification of Failures Occurring on a System on Chip Exposed to a Neutron Beam for Safety Applications
Authors: S. Thomet, S. De-Paoli, F. Ghaffari, J. M. Daveau, P. Roche, O. Romain
Abstract:
In this paper, we present a hardware module dedicated to understanding the fail reason of a System on Chip (SoC) exposed to a particle beam. Impact of Single-Event Effects (SEE) on processor-based SoCs is a concern that has increased in the past decade, particularly for terrestrial applications with automotive safety increasing requirements, as well as consumer and industrial domains. The SEE created by the impact of a particle on an SoC may have consequences that can end to instability or crashes. Specific hardening techniques for hardware and software have been developed to make such systems more reliable. SoC is then qualified using cosmic ray Accelerated Soft-Error Rate (ASER) to ensure the Soft-Error Rate (SER) remains in mission profiles. Understanding where errors are occurring is another challenge because of the complexity of operations performed in an SoC. Common techniques to monitor an SoC running under a beam are based on non-intrusive debug, consisting of recording the program counter and doing some consistency checking on the fly. To detect and understand SEE, we have developed a module embedded within the SoC that provide support for recording probes, hardware watchpoints, and a memory mapped register bank dedicated to software usage. To identify CPU failure modes and the most important resources to probe, we have carried out a fault injection campaign on the RTL model of the SoC. Probes are placed on generic CPU registers and bus accesses. They highlight the propagation of errors and allow identifying the failure modes. Typical resulting errors are bit-flips in resources creating bad addresses, illegal instructions, longer than expected loops, or incorrect bus accesses. Although our module is processor agnostic, it has been interfaced to a RISC-V by probing some of the processor registers. Probes are then recorded in a ring buffer. Associated hardware watchpoints are allowing to do some control, such as start or stop event recording or halt the processor. Finally, the module is also providing a bank of registers where the firmware running on the SoC can log information. Typical usage is for operating system context switch recording. The module is connected to a dedicated debug bus and is interfaced to a remote controller via a debugger link. Thus, a remote controller can interact with the monitoring module without any intrusiveness on the SoC. Moreover, in case of CPU unresponsiveness, or system-bus stall, the recorded information can still be recovered, providing the fail reason. A preliminary version of the module has been integrated into a test chip currently being manufactured at ST in 28-nm FDSOI technology. The module has been triplicated to provide reliable information on the SoC behavior. As the primary application domain is automotive and safety, the efficiency of the module will be evaluated by exposing the test chip under a fast-neutron beam by the end of the year. In the meantime, it will be tested with alpha particles and electromagnetic fault injection (EMFI). We will report in the paper on fault-injection results as well as irradiation results.Keywords: fault injection, SoC fail reason, SoC soft error rate, terrestrial application
Procedia PDF Downloads 22610 Use of Zikani’s Ribosome Modulating Agents for Treating Recessive Dystrophic & Junctional Epidermolysis Bullosa with Nonsense Mutations
Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur
Abstract:
Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation
Procedia PDF Downloads 959 Optical Imaging Based Detection of Solder Paste in Printed Circuit Board Jet-Printing Inspection
Authors: D. Heinemann, S. Schramm, S. Knabner, D. Baumgarten
Abstract:
Purpose: Applying solder paste to printed circuit boards (PCB) with stencils has been the method of choice over the past years. A new method uses a jet printer to deposit tiny droplets of solder paste through an ejector mechanism onto the board. This allows for more flexible PCB layouts with smaller components. Due to the viscosity of the solder paste, air blisters can be trapped in the cartridge. This can lead to missing solder joints or deviations in the applied solder volume. Therefore, a built-in and real-time inspection of the printing process is needed to minimize uncertainties and increase the efficiency of the process by immediate correction. The objective of the current study is the design of an optimal imaging system and the development of an automatic algorithm for the detection of applied solder joints from optical from the captured images. Methods: In a first approach, a camera module connected to a microcomputer and LED strips are employed to capture images of the printed circuit board under four different illuminations (white, red, green and blue). Subsequently, an improved system including a ring light, an objective lens, and a monochromatic camera was set up to acquire higher quality images. The obtained images can be divided into three main components: the PCB itself (i.e., the background), the reflections induced by unsoldered positions or screw holes and the solder joints. Non-uniform illumination is corrected by estimating the background using a morphological opening and subtraction from the input image. Image sharpening is applied in order to prevent error pixels in the subsequent segmentation. The intensity thresholds which divide the main components are obtained from the multimodal histogram using three probability density functions. Determining the intersections delivers proper thresholds for the segmentation. Remaining edge gradients produces small error areas which are removed by another morphological opening. For quantitative analysis of the segmentation results, the dice coefficient is used. Results: The obtained PCB images show a significant gradient in all RGB channels, resulting from ambient light. Using different lightings and color channels 12 images of a single PCB are available. A visual inspection and the investigation of 27 specific points show the best differentiation between those points using a red lighting and a green color channel. Estimating two thresholds from analyzing the multimodal histogram of the corrected images and using them for segmentation precisely extracts the solder joints. The comparison of the results to manually segmented images yield high sensitivity and specificity values. Analyzing the overall result delivers a Dice coefficient of 0.89 which varies for single object segmentations between 0.96 for a good segmented solder joints and 0.25 for single negative outliers. Conclusion: Our results demonstrate that the presented optical imaging system and the developed algorithm can robustly detect solder joints on printed circuit boards. Future work will comprise a modified lighting system which allows for more precise segmentation results using structure analysis.Keywords: printed circuit board jet-printing, inspection, segmentation, solder paste detection
Procedia PDF Downloads 3308 Environmentally Sustainable Transparent Wood: A Fully Green Approach from Bleaching to Impregnation for Energy-Efficient Engineered Wood Components
Authors: Francesca Gullo, Paola Palmero, Massimo Messori
Abstract:
Transparent wood is considered a promising structural material for the development of environmentally friendly, energy-efficient engineered components. To obtain transparent wood from natural wood materials two approaches can be used: i) bottom-up and ii) top-down. Through the second method, the color of natural wood samples is lightened through a chemical bleaching process that acts on chromophore groups of lignin, such as the benzene ring, quinonoid, vinyl, phenolics, and carbonyl groups. These chromophoric units form complex conjugate systems responsible for the brown color of wood. There are two strategies to remove color and increase the whiteness of wood: i) lignin removal and ii) lignin bleaching. In the lignin removal strategy, strong chemicals containing chlorine (chlorine, hypochlorite, and chlorine dioxide) and oxidizers (oxygen, ozone, and peroxide) are used to completely destroy and dissolve the lignin. In lignin bleaching methods, a moderate reductive (hydrosulfite) or oxidative (hydrogen peroxide) is commonly used to alter or remove the groups and chromophore systems of lignin, selectively discoloring the lignin while keeping the macrostructure intact. It is, therefore, essential to manipulate nanostructured wood by precisely controlling the nanopores in the cell walls by monitoring both chemical treatments and process conditions, for instance, the treatment time, the concentration of chemical solutions, the pH value, and the temperature. The elimination of wood light scattering is the second step in the fabrication of transparent wood materials, which can be achieved through two-step approaches: i) the polymer impregnation method and ii) the densification method. For the polymer impregnation method, the wood scaffold is treated with polymers having a corresponding refractive index (e.g., PMMA and epoxy resins) under vacuum to obtain the transparent composite material, which can finally be pressed to align the cellulose fibers and reduce interfacial defects in order to have a finished product with high transmittance (>90%) and excellent light-guiding. However, both the solution-based bleaching and the impregnation processes used to produce transparent wood generally consume large amounts of energy and chemicals, including some toxic or pollutant agents, and are difficult to scale up industrially. Here, we report a method to produce optically transparent wood by modifying the lignin structure with a chemical reaction at room temperature using small amounts of hydrogen peroxide in an alkaline environment. This method preserves the lignin, which results only deconjugated and acts as a binder, providing both a strong wood scaffold and suitable porosity for infiltration of biobased polymers while reducing chemical consumption, the toxicity of the reagents used, polluting waste, petroleum by-products, energy and processing time. The resulting transparent wood demonstrates high transmittance and low thermal conductivity. Through the combination of process efficiency and scalability, the obtained materials are promising candidates for application in the field of construction for modern energy-efficient buildings.Keywords: bleached wood, energy-efficient components, hydrogen peroxide, transparent wood, wood composites
Procedia PDF Downloads 427 Sensorless Machine Parameter-Free Control of Doubly Fed Reluctance Wind Turbine Generator
Authors: Mohammad R. Aghakashkooli, Milutin G. Jovanovic
Abstract:
The brushless doubly-fed reluctance generator (BDFRG) is an emerging, medium-speed alternative to a conventional wound rotor slip-ring doubly-fed induction generator (DFIG) in wind energy conversion systems (WECS). It can provide competitive overall performance and similar low failure rates of a typically 30% rated back-to-back power electronics converter in 2:1 speed ranges but with the following important reliability and cost advantages over DFIG: the maintenance-free operation afforded by its brushless structure, 50% synchronous speed with the same number of rotor poles (allowing the use of a more compact, and more efficient two-stage gearbox instead of a vulnerable three-stage one), and superior grid integration properties including simpler protection for the low voltage ride through compliance of the fractional converter due to the comparatively higher leakage inductances and lower fault currents. Vector controlled pulse-width-modulated converters generally feature a much lower total harmonic distortion relative to hysteresis counterparts with variable switching rates and as such have been a predominant choice for BDFRG (and DFIG) wind turbines. Eliminating a shaft position sensor, which is often required for control implementation in this case, would be desirable to address the associated reliability issues. This fact has largely motivated the recent growing research of sensorless methods and developments of various rotor position and/or speed estimation techniques for this purpose. The main limitation of all the observer-based control approaches for grid-connected wind power applications of the BDFRG reported in the open literature is the requirement for pre-commissioning procedures and prior knowledge of the machine inductances, which are usually difficult to accurately identify by off-line testing. A model reference adaptive system (MRAS) based sensor-less vector control scheme to be presented will overcome this shortcoming. The true machine parameter independence of the proposed field-oriented algorithm, offering robust, inherently decoupled real and reactive power control of the grid-connected winding, is achieved by on-line estimation of the inductance ratio, the underlying rotor angular velocity and position MRAS observer being reliant upon. Such an observer configuration will be more practical to implement and clearly preferable to the existing machine parameter dependent solutions, and especially bearing in mind that with very little modifications it can be adapted for commercial DFIGs with immediately obvious further industrial benefits and prospects of this work. The excellent encoder-less controller performance with maximum power point tracking in the base speed region will be demonstrated by realistic simulation studies using large-scale BDFRG design data and verified by experimental results on a small laboratory prototype of the WECS emulation facility.Keywords: brushless doubly fed reluctance generator, model reference adaptive system, sensorless vector control, wind energy conversion
Procedia PDF Downloads 596 Numerical Prediction of Width Crack of Concrete Dapped-End Beams
Authors: Jatziri Y. Moreno-Martinez, Arturo Galvan, Xavier Chavez Cardenas, Hiram Arroyo
Abstract:
Several methods have been utilized to study the prediction of cracking of concrete structural under loading. The finite element analysis is an alternative that shows good results. The aim of this work was the numerical study of the width crack in reinforced concrete beams with dapped ends, these are frequently found in bridge girders and precast concrete construction. Properly restricting cracking is an important aspect of the design in dapped ends, it has been observed that the cracks that exceed the allowable widths are unacceptable in an aggressive environment for reinforcing steel. For simulating the crack width, the discrete crack approach was considered by means of a Cohesive Zone (CZM) Model using a function to represent the crack opening. Two cases of dapped-end were constructed and tested in the laboratory of Structures and Materials of Engineering Institute of UNAM. The first case considers a reinforcement based on hangers as well as on vertical and horizontal ring, the second case considers 50% of the vertical stirrups in the dapped end to the main part of the beam were replaced by an equivalent area (vertically projected) of diagonal bars under. The loading protocol consisted on applying symmetrical loading to reach the service load. The models were performed using the software package ANSYS v. 16.2. The concrete structure was modeled using three-dimensional solid elements SOLID65 capable of cracking in tension and crushing in compression. Drucker-Prager yield surface was used to include the plastic deformations. The reinforcement was introduced with smeared approach. Interface delamination was modeled by traditional fracture mechanics methods such as the nodal release technique adopting softening relationships between tractions and the separations, which in turn introduce a critical fracture energy that is also the energy required to break apart the interface surfaces. This technique is called CZM. The interface surfaces of the materials are represented by a contact elements Surface-to-Surface (CONTA173) with bonded (initial contact). The Mode I dominated bilinear CZM model assumes that the separation of the material interface is dominated by the displacement jump normal to the interface. Furthermore, the opening crack was taken into consideration according to the maximum normal contact stress, the contact gap at the completion of debonding, and the maximum equivalent tangential contact stress. The contact elements were placed in the crack re-entrant corner. To validate the proposed approach, the results obtained with the previous procedure are compared with experimental test. A good correlation between the experimental and numerical Load-Displacement curves was presented, the numerical models also allowed to obtain the load-crack width curves. In these two cases, the proposed model confirms the capability of predicting the maximum crack width, with an error of ± 30 %. Finally, the orientation of the crack is a fundamental for the prediction of crack width. The results regarding the crack width can be considered as good from the practical point view. Load-Displacement curve of the test and the location of the crack were able to obtain favorable results.Keywords: cohesive zone model, dapped-end beams, discrete crack approach, finite element analysis
Procedia PDF Downloads 1615 Infrared Spectroscopy Fingerprinting of Herbal Products- Application of the Hypericum perforatum L. Supplements
Authors: Elena Iacob, Marie-Louise Ionescu, Elena Ionescu, Carmen Elena Tebrencu, Oana Teodora Ciuperca
Abstract:
Infrared spectroscopy (FT-IR) is an advanced technique frequently used to authenticate both raw materials and final products using their specific fingerprints and to determine plant extracts biomarkers based on their functional groups. In recent years the market for Hypericum has grown rapidly and also has grown the cases of adultery/replacement, especially for Hypericum perforatum L.specie. Presence/absence of same biomarkers provides preliminary identification of Hypericum species in safe use in the manufacture of food supplements. The main objective of the work was to characterize the main biomarkers of Hypericum perforatum L. (St. John's wort) and identify this species in herbal food supplements after specific FT-IR fingerprint. An experimental program has been designed in order to test: (1) raw material (St. John's wort); (2)intermediate raw materials (St. John's wort dry extract ); (3) the finished products: tablets based on powders, on extracts, on powder and extract, hydroalcoholic solution from herbal mixture based on St. John's wort. The analyze using FTIR infrared spectroscopy were obtained raw materials, intermediates and finished products spectra, respectively absorption bands corresponding and similar with aliphatic and aromatic structures; examination was done individually and through comparison between Hypericum perforatum L. plant species and finished product The tests were done in correlation with phytochemical markers for authenticating the specie Hypericum perforatum L.: hyperoside, rutin, quercetin, isoquercetin, luteolin, apigenin, hypericin, hyperforin, chlorogenic acid. Samples were analyzed using a Shimatzu FTIR spectrometer and the infrared spectrum of each sample was recorded in the MIR region, from 4000 to 1000 cm-1 and then the fingerprint region was selected for data analysis. The following functional groups were identified -stretching vibrations suggests existing groups in the compounds of interest (flavones–rutin, hyperoside, polyphenolcarboxilic acids - chlorogenic acid, naphtodianthrones- hypericin): oxidril groups (OH) free alcohol type: rutin, hyperoside, chlorogenic acid; C = O bond from structures with free carbonyl groups of aldehyde, ketone, carboxylic, ester: hypericin; C = O structure with the free carbonyl of the aldehyde groups, ketone, carboxylic acid, esteric/C = O free bonds present in chlorogenic acid; C = C bonds of the aromatic ring (condensed aromatic hydrocarbons, heterocyclic compounds) present in all compounds of interest; OH phenolic groups: present in all compounds of interest, C-O-C groups from glycoside structures: rutin, hyperoside, chlorogenic acid. The experimental results show that: (I)The six fingerprint region analysis indicated the presence of specific functional groups: (1) 1000 - 1130 cm-1 (C-O–C of glycoside structures); (2) 1200-1380 cm-1 (carbonyl C-O or O-H phenolic); (3) 1400-1450 cm-1 (C=C aromatic); (4) 1600- 1730 cm-1 (C=O carbonyl); (5) 2850 - 2930 cm-1 (–CH3, -CH2-, =CH-); (6) 338-3920 cm-1 (OH free alcohol type); (II)Comparative FT-IR spectral analysis indicate the authenticity of the finished products ( tablets) in terms of Hypericum perforatum L. content; (III)The infrared spectroscopy is an adequate technique for identification and authentication of the medicinal herbs , intermediate raw material and in the food supplements less in the form of solutions where the results are not conclusive.Keywords: Authentication, FT-IR fingerprint, Herbal supplements, Hypericum perforatum L.
Procedia PDF Downloads 3664 HydroParks: Directives for Physical Environment Interventions Battling Childhood Overweight in Berlin, Germany
Authors: Alvaro Valera Sosa
Abstract:
Background: In recent years, childhood overweight and obesity have become an increasing and challenging phenomenon in Berlin and Germany in general. The highest shares of childhood overweight in Berlin are district localities within the inner city ring with lowest socio-economic levels and the highest number of migration background populations. Most factors explaining overweight and obesity are linked to individual dispositions and nutrition balances. Among various strategies, to target drinking behaviors of children and adolescents has been proven to be effective. On the one hand, encouraging the intake of water – which does not contain energy and thus may support a healthy weight status – on the other hand, reducing the consumption of sugar-containing beverages – which are linked to weight gain and obesity. Anyhow, these preventive approaches have mostly developed into individual or educational interventions widely neglecting environmental modifications. Therefore, little is known on how urban physical environment patterns and features can act as influence factors for childhood overweight. Aiming the development of a physical environment intervention tackling children overweight, this study evaluated urban situations surrounding public playgrounds in Berlin where the issue is evident. It verified the presence and state of physical environmental conditions that can be conducive for children to engage physical activity and water intake. Methods: The study included public playgrounds for children from 0-12 y/o within district localities with the highest prevalence of childhood overweight, highest population density, and highest mixed uses. A systematic observation was realized to describe physical environment patterns and features that may affect children health behavior leading to overweight. Neighborhood walkability for all age groups was assessed using the Walkability for Health framework (TU-Berlin). Playground physical environment conditions were evaluated using Active Living Research assessment sheets. Finally, the food environment in the playground’s pedestrian catchment areas was reviewed focusing on: proximity to suppliers offering sugar-containing beverages, and physical access for 5 y/o children and up to drinking water following the Drinking Fountains and Public Health guidelines of the Pacific Institute. Findings: Out of 114 locations, only 7 had a child population over 3.000. Three with the lowest socio-economic index and highest percentage of migration background were selected. All three urban situations presented similar walkability: large trafficked avenues without buffer bordering at least one side of the playground, and important block to block disconnections for active travel. All three playgrounds rated equipment conditions from good to very good. None had water fountains at the reach of a 5 y/o. and all presented convenience stores and/or fast food outlets selling sugar-containing beverages nearby the perimeter. Conclusion: The three playground situations selected are representative of Berlin locations where most factors that influence children overweight are found. The results delivered urban and architectural design directives for an environmental intervention, used to study children health-related behavior. A post-intervention evaluation could prove associations between designed spaces and children overweight rate reduction creating a precedent in public health interventions and providing novel strategies for the health sector.Keywords: children overweight, evaluation research, public playgrounds, urban design, urban health
Procedia PDF Downloads 1513 Deep Learning Based on Image Decomposition for Restoration of Intrinsic Representation
Authors: Hyohun Kim, Dongwha Shin, Yeonseok Kim, Ji-Su Ahn, Kensuke Nakamura, Dongeun Choi, Byung-Woo Hong
Abstract:
Artefacts are commonly encountered in the imaging process of clinical computed tomography (CT) where the artefact refers to any systematic discrepancy between the reconstructed observation and the true attenuation coefficient of the object. It is known that CT images are inherently more prone to artefacts due to its image formation process where a large number of independent detectors are involved, and they are assumed to yield consistent measurements. There are a number of different artefact types including noise, beam hardening, scatter, pseudo-enhancement, motion, helical, ring, and metal artefacts, which cause serious difficulties in reading images. Thus, it is desired to remove nuisance factors from the degraded image leaving the fundamental intrinsic information that can provide better interpretation of the anatomical and pathological characteristics. However, it is considered as a difficult task due to the high dimensionality and variability of data to be recovered, which naturally motivates the use of machine learning techniques. We propose an image restoration algorithm based on the deep neural network framework where the denoising auto-encoders are stacked building multiple layers. The denoising auto-encoder is a variant of a classical auto-encoder that takes an input data and maps it to a hidden representation through a deterministic mapping using a non-linear activation function. The latent representation is then mapped back into a reconstruction the size of which is the same as the size of the input data. The reconstruction error can be measured by the traditional squared error assuming the residual follows a normal distribution. In addition to the designed loss function, an effective regularization scheme using residual-driven dropout determined based on the gradient at each layer. The optimal weights are computed by the classical stochastic gradient descent algorithm combined with the back-propagation algorithm. In our algorithm, we initially decompose an input image into its intrinsic representation and the nuisance factors including artefacts based on the classical Total Variation problem that can be efficiently optimized by the convex optimization algorithm such as primal-dual method. The intrinsic forms of the input images are provided to the deep denosing auto-encoders with their original forms in the training phase. In the testing phase, a given image is first decomposed into the intrinsic form and then provided to the trained network to obtain its reconstruction. We apply our algorithm to the restoration of the corrupted CT images by the artefacts. It is shown that our algorithm improves the readability and enhances the anatomical and pathological properties of the object. The quantitative evaluation is performed in terms of the PSNR, and the qualitative evaluation provides significant improvement in reading images despite degrading artefacts. The experimental results indicate the potential of our algorithm as a prior solution to the image interpretation tasks in a variety of medical imaging applications. This work was supported by the MISP(Ministry of Science and ICT), Korea, under the National Program for Excellence in SW (20170001000011001) supervised by the IITP(Institute for Information and Communications Technology Promotion).Keywords: auto-encoder neural network, CT image artefact, deep learning, intrinsic image representation, noise reduction, total variation
Procedia PDF Downloads 1872 Capsaicin Derivatives Enhanced Activity of α1β2γ2S-Aminobutyric Acid Type a Receptor Expressed in Xenopus laevis Oocytes
Authors: Jia H. Wong, Jingli Zhang, Habsah Mohamad, Iswatun H. Abdullah Ripain, Muhammad Bilal, Amelia J. Lloyd, Abdul A. Mohamed Yusoff, Jafri M. Abdullah
Abstract:
Epilepsy is one of the most common neurological diseases affecting more than 50 million of people worldwide. Epilepsy is a state of recurrent, spontaneous seizures with multiple syndromes and symptoms of different causes of brain dysfunction, prognosis, and treatments; characterized by transient, occasional and stereotyped interruptions of behavior whereby the excitatory-inhibitory activities within the central nervous system (CNS) are thrown out of balance due to various kinds of interferences. The goal of antiepileptic treatment is to enable patients to be free from seizures or to achieve control of seizures through surgical treatment and/or pharmacotherapy. Pharmacotherapy through AED plays an important role especially in countries with epilepsy treatment gap due to costs and availability of health facilities, skills and resources, yet there are about one-third of the people with epilepsy have drug-resistant seizures. Hence, this poses considerable challenges to the healthcare system and the effort in providing cost-effective treatment as well as the search for alternatives to treatment and management of epilepsy. Enhancement of γ-aminobutyric acid (GABA)-mediated inhibitory neurotransmission is one of the key mechanisms of actions of antiepileptic drugs. GABA type > a receptors (GABAAR) are ligand-gated ion channels that mediate rapid inhibitory neurotransmission upon the binding of GABA with a heteropentameric structure forming a central pore that is permeable to the influx of chloride ions in its activated state. The major isoform of GABAA receptors consists of two α1, two β2, and one γ2 subunit. It is the most abundantly expressed combinations in the brain and the most commonly researched through Xenopus laevis oocytes. With the advancing studies on ethnomedicine and traditional treatments using medicinal plants, increasing evidence reveal that spice and herb plants with medicinal properties play an important role in the treatment of ailments within communities across different cultures. Capsaicin is the primary natural capsaicinoid in hot peppers of plant genus Capsicum, consist of an aromatic ring, an amide linkage and a hydrophobic side chain. The study showed that capsaicins conferred neuroprotection in status epilepticus mouse models through anti-ictogenic, hypothermic, antioxidative, anti-inflammatory, and anti-apoptotic actions in a dose-dependent manner. In this study, five capsaicin derivatives were tested for their ability to increase the GABA-induced chloride current on α1β2γ2S of GABAAR expressed on Xenopus laevis oocytes using the method of two-microelectrode voltage clamp. Two of the capsaicin derivatives, IS5 (N-(4-hydroxy-3-methoxybenzyl)-3-methylbutyramide) and IS10 (N-(4-hydroxy-3-methoxybenzyl)-decanamide) at a concentration of 30µM were able to significantly increase the GABA-induced chloride current with p=0.002 and p=0.026 respectively. This study were able to show the enhancement effect of two capsaicin derivatives with moderate length of hydrocarbon chain on this receptor subtype, revealing the promising inhibitory activity of capsaicin derivatives through enhancement of GABA-induced chloride current and further investigations should be carried out to verify its antiepileptic effects in animal models.Keywords: α1β2γ2 GABAA receptors, α1β2γ2S, antiepileptic, capsaicin derivatives, two-microelectrode voltage clamp, Xenopus laevis oocytes
Procedia PDF Downloads 3561 Morphological and Molecular Abnormalities of the Skeletal Muscle Tissue from Pediatric Patient Affected by a Rare Genetic Chaperonopathy Associated with Motor Neuropathy
Authors: Leila Noori, Rosario Barone, Francesca Rappa, Antonella Marino Gammazza, Alessandra Maria Vitale, Giuseppe Donato Mangano, Giusy Sentiero, Filippo Macaluso, Kathryn H. Myburgh, Francesco Cappello, Federica Scalia
Abstract:
The neuromuscular system controls, directs, and allows movement of the body through the action of neural circuits, which include motor neurons, sensory neurons, and skeletal muscle fibers. Protein homeostasis of the involved cytotypes appears crucial to maintain the correct and prolonged functions of the neuromuscular system, and both neuronal cells and skeletal muscle fibers express significant quantities of protein chaperones, the molecular machinery responsible to maintain the protein turnover. Genetic mutations or defective post-translational modifications of molecular chaperones (i.e., genetic or acquired chaperonopathies) may lead to neuromuscular disorders called as neurochaperonopathies. The limited knowledge of the effects of the defective chaperones on skeletal muscle fibers and neurons impedes the progression of therapeutic approaches. A distinct genetic variation of CCT5 gene encoding for the subunit 5 of the chaperonin CCT (Chaperonin Containing TCP1; also known as TRiC, TCP1 Ring Complex) was recently described associated with severe distal motor neuropathy by our team. In this study, we investigated the histopathological abnormalities of the skeletal muscle biopsy of the pediatric patient affected by the mutation Leu224Val in the CCT5 subunit. We provide molecular and structural features of the diseased skeletal muscle tissue that we believe may be useful to identify undiagnosed cases of this rare genetic disorder. We investigated the histological abnormalities of the affected tissue via hematoxylin and eosin staining. Then we used immunofluorescence and qPCR techniques to explore the expression and distribution of CCT5 in diseased and healthy skeletal muscle tissue. Immunofluorescence and immunohistochemistry assays were performed to study the sarcomeric and structural proteins of skeletal muscle, including actin, myosin, tubulin, troponin-T, telethonin, and titin. We performed Western blot to examine the protein expression of CCT5 and some heat shock proteins, Hsp90, Hsp60, Hsp27, and α-B crystallin, along with the main client proteins of the CCT5, actin, and tubulin. Our findings revealed muscular atrophy, abnormal morphology, and different sizes of muscle fibers in affected tissue. The swollen nuclei and wide interfiber spaces were seen. Expression of CCT5 had been decreased and showed a different distribution pattern in the affected tissue. Altered expression, distribution, and bandage pattern were detected by confocal microscopy for the interested muscular proteins in tissue from the patient compared to the healthy control. Protein levels of the studied Hsps normally located at the Z-disk were reduced. Western blot results showed increased levels of the actin and tubulin proteins in the diseased skeletal muscle biopsy compared to healthy tissue. Chaperones must be expressed at high levels in skeletal muscle to counteract various stressors such as mechanical, oxidative, and thermal crises; therefore, it seems relevant that defects of molecular chaperones may result in damaged skeletal muscle fibers. So far, several chaperones or cochaperones involved in neuromuscular disorders have been defined. Our study shows that alteration of the CCT5 subunit is associated with the damaged structure of skeletal muscle fibers and alterations of chaperone system components and paves the way to explore possible alternative substrates of chaperonin CCT. However, further studies are underway to investigate the CCT mechanisms of action to design applicable therapeutic strategies.Keywords: molecular chaperones, neurochaperonopathy, neuromuscular system, protein homeostasis
Procedia PDF Downloads 65